Saitow F, Satake S, Yamada J, Konishi S
Laboratory of Molecular Neurobiology, Mitsubishi Kasei Institute of Life Sciences and CREST, JST (Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation), Tokyo 194-8511, Japan.
J Neurophysiol. 2000 Oct;84(4):2016-25. doi: 10.1152/jn.2000.84.4.2016.
Norepinephrine (NE) has been shown to elicit long-term facilitation of GABAergic transmission to rat cerebellar Purkinje cells (PCs) through beta-adrenergic receptor activation. To further examine the locus and adrenoceptor subtypes involved in the NE-induced facilitation of GABAergic transmission, we recorded inhibitory postsynaptic currents (IPSCs) evoked by focal stimulation with paired-pulse (PP) stimuli from PCs in rat cerebellar slices by whole cell recordings and analyzed the PP ratio of the IPSC amplitude. NE increased the IPSC amplitude with a decease in the variance of the PP ratio, which was mimicked by presynaptic manipulation of the transmission caused by increasing the extracellular Ca(2+) concentration, confirming that the presynaptic adrenergic receptors are responsible for the facilitation. Pharmacological tests showed that the beta(2)-adrenoceptor antagonist, ICI118,551, but not the beta(1)-adrenoceptor antagonist, CGP20712A, blocked the NE-induced IPSC facilitation, suggesting that the beta(2)-adrenoceptors on cerebellar interneurons, basket cells (BCs), mediate the noradrenergic facilitation of GABAergic transmission. Double recordings were performed from BCs and PCs to further characterize the regulation of the GABAergic synapses. First, on-cell recordings from BCs showed that the beta-agonist isoproterenol (ISP) increased the frequencies of the spontaneous spikes in BCs and the spike-triggered IPSCs in PCs recorded with the whole cell mode. The amplitude of the spike-triggered IPSCs decreased or increased depending on the individual GABAergic synapses examined. Forskolin invariably increased both the amplitude and the frequency of the spike-triggered IPSCs. Double whole cell recordings from BC-PC pairs showed that ISP mainly caused an increase in the amplitude of the IPSCs evoked in the PCs by an action current in the BCs produced in response to voltage steps from -60 to -10 mV. Our data suggest that the noradrenergic facilitation of GABAergic transmission in the rat cerebellar cortex is mediated, at least in part, by depolarization and action potential discharges in the BCs through activation of the beta(2)-adrenoceptors in BCs coupled to intracellular cyclic AMP formation.
去甲肾上腺素（NE）已被证明可通过β-肾上腺素能受体激活，引发对大鼠小脑浦肯野细胞（PCs）的GABA能传递的长期易化作用。为了进一步研究参与NE诱导的GABA能传递易化作用的位点和肾上腺素能受体亚型，我们通过全细胞记录，在大鼠小脑切片中，记录了来自PCs的局灶性刺激与配对脉冲（PP）刺激诱发的抑制性突触后电流（IPSCs），并分析了IPSC幅度的PP比率。NE增加了IPSC幅度，同时PP比率的方差减小，增加细胞外Ca(2+)浓度引起的突触传递的突触前操作模拟了这种情况，证实突触前肾上腺素能受体负责这种易化作用。药理学测试表明，β(2)-肾上腺素能受体拮抗剂ICI118,551可阻断NE诱导的IPSC易化作用，而β(1)-肾上腺素能受体拮抗剂CGP20712A则不能，这表明小脑中间神经元篮状细胞（BCs）上的β(2)-肾上腺素能受体介导了去甲肾上腺素能对GABA能传递的易化作用。对BCs和PCs进行双记录，以进一步表征GABA能突触的调节。首先，对BCs进行的细胞贴附记录表明，β-激动剂异丙肾上腺素（ISP）增加了BCs中自发动作电位的频率以及全细胞模式下记录的PCs中动作电位触发的IPSCs。动作电位触发的IPSCs的幅度根据所检查的单个GABA能突触而降低或增加。福斯高林总是增加动作电位触发的IPSCs的幅度和频率。对BC-PC对进行的双全细胞记录表明，ISP主要通过BCs中响应从-60 mV到-10 mV的电压阶跃产生的动作电流，使PCs中诱发的IPSCs幅度增加。我们的数据表明，大鼠小脑皮质中去甲肾上腺素能对GABA能传递的易化作用至少部分是通过BCs中的去极化和动作电位发放介导的，这是通过激活BCs中与细胞内环磷酸腺苷形成偶联的β(2)-肾上腺素能受体实现的。
